| First Author | Ren DN | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6906 | PubMed ID | 25902418 |
| Mgi Jnum | J:222690 | Mgi Id | MGI:5645393 |
| Doi | 10.1038/ncomms7906 | Citation | Ren DN, et al. (2015) LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis. Nat Commun 6:6906 |
| abstractText | How Wnt signalling including canonical and non-canonical pathways are initiated at the cell surface is not completely understood. Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain. Importantly, through direct binding to Frz, LRP5/6 are able to prevent Frz-regulated non-canonical pathway activation and further non-canonical pathway-mediated tumour metastasis. Knockdown of endogenous LRP5/6 promotes otherwise-nonaggressive tumour cells to migrate in vitro, whereas a soluble recombinant protein of LRP6 ectodomain suppresses migration and metastasis of otherwise-aggressive tumour cells in vitro and in vivo. Furthermore, the expression level of membrane LRP5/6 correlates inversely with metastasis in mouse and human breast cancer. Our study suggests a previously unrecognized mode of receptor interaction, revealing the mechanism of LRP5/6 in inhibition of non-canonical pathway, and a possible clinical use of the LRP6 ectodomain to impede metastasis. |
